Stroke is the third leading cause of death in the U.S., affecting at least 500,000 patients annually, and is considered the most common cause of adult disability. Pharmacological intervention has made little, if any, impact on preventing neurological damage once a stroke has occurred. Reactive oxygen species (ROS), which mediate tissue damage in numerous pathologies, have been implicated in the neurological damage resulting from stroke. Eukarion has developed a class of synthetic molecules that are catalytic ROS scavengers, mimicking the endogenous antioxidant enzymes SOD and catalase. One of these compounds, EUK-134, is highly protective in a rodent model for stroke, even when administered three hours after the onset of brain ischemia. This project will investigate the potential therapeutic value of these compounds for stroke. The specific aims are: (1) To characterize the catalytic and chemical properties of the compounds, focusing on those to be tested in vivo; (2) To further characterize the efficacy of EUK-134 with respect to their effectiveness in the stroke model. The overall goal of this Phase I project is to select candidate(s) for future preclinical and clinical development as therapeutic agents for stroke. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE